Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2
Abstract The adipose tissue is regarded as an endocrine organ and secretes bioactive adipokines modulating chronic inflammation and oxidative stress in obesity. Gal-9 is secreted out upon cell injuries, interacts with T-cell immunoglobulin-3 (Tim-3) and induces apoptosis in activated Th1 cells. Gal-...
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doaj-110c99ec57ae431286337d47e898548a2021-03-21T12:37:56ZengNature Publishing GroupScientific Reports2045-23222021-03-0111111210.1038/s41598-021-85080-1Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2Tomokazu Nunoue0Satoshi Yamaguchi1Sanae Teshigawara2Akihiro Katayama3Atsuko Nakatsuka4Jun Eguchi5Toshiro Niki6Jun Wada7Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDepartment of Immunology, Kagawa UniversityDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAbstract The adipose tissue is regarded as an endocrine organ and secretes bioactive adipokines modulating chronic inflammation and oxidative stress in obesity. Gal-9 is secreted out upon cell injuries, interacts with T-cell immunoglobulin-3 (Tim-3) and induces apoptosis in activated Th1 cells. Gal-9 also binds to protein disulfide isomerase (PDI), maintains PDI on surface of T cells, and increases free thiols in the disulfide/thiol cycles. To explore the molecular mechanism of obesity, we investigated Gal-9−/− and Gal-9wt/wt C57BL/6J mice fed with high fat-high sucrose (HFHS) chow. Gal-9−/− mice were resistant to diet-induced obesity associated with reduction of epididymal and mesenteric fat tissues and improved glucose tolerance compared with Gal-9wt/wt mice. However, the number of M1, M2 macrophages, and M1/M2 ratio in epididymal fat were unaltered. Under HFHS chow, Gal-9−/− mice receiving Gal-9−/− or Gal-9wt/wt bone marrow-derived cells (BMCs) demonstrated significantly lower body weight compared with Gal-9wt/wt mice receiving Gal-9−/− BMCs. We identified the binding between Gal-9 and peroxiredoxin-2 (PRDX2) in sugar chain-independent manner by nanoLC-MS/MS, immunoprecipitation, and pull-down assay. In 3T3L1 adipocytes, Gal-9 knockdown shifts PRDX2 monomer (reduced form) dominant from PRDX2 dimer (oxidized form) under oxidative stress with H2O2. The inhibition of Gal-9 in adipocytes may be a new therapeutic approach targeting the oxidative stress and subsequent glucose intolerance in obesity.https://doi.org/10.1038/s41598-021-85080-1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tomokazu Nunoue Satoshi Yamaguchi Sanae Teshigawara Akihiro Katayama Atsuko Nakatsuka Jun Eguchi Toshiro Niki Jun Wada |
spellingShingle |
Tomokazu Nunoue Satoshi Yamaguchi Sanae Teshigawara Akihiro Katayama Atsuko Nakatsuka Jun Eguchi Toshiro Niki Jun Wada Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2 Scientific Reports |
author_facet |
Tomokazu Nunoue Satoshi Yamaguchi Sanae Teshigawara Akihiro Katayama Atsuko Nakatsuka Jun Eguchi Toshiro Niki Jun Wada |
author_sort |
Tomokazu Nunoue |
title |
Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2 |
title_short |
Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2 |
title_full |
Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2 |
title_fullStr |
Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2 |
title_full_unstemmed |
Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2 |
title_sort |
lgals9 deficiency ameliorates obesity by modulating redox state of prdx2 |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-03-01 |
description |
Abstract The adipose tissue is regarded as an endocrine organ and secretes bioactive adipokines modulating chronic inflammation and oxidative stress in obesity. Gal-9 is secreted out upon cell injuries, interacts with T-cell immunoglobulin-3 (Tim-3) and induces apoptosis in activated Th1 cells. Gal-9 also binds to protein disulfide isomerase (PDI), maintains PDI on surface of T cells, and increases free thiols in the disulfide/thiol cycles. To explore the molecular mechanism of obesity, we investigated Gal-9−/− and Gal-9wt/wt C57BL/6J mice fed with high fat-high sucrose (HFHS) chow. Gal-9−/− mice were resistant to diet-induced obesity associated with reduction of epididymal and mesenteric fat tissues and improved glucose tolerance compared with Gal-9wt/wt mice. However, the number of M1, M2 macrophages, and M1/M2 ratio in epididymal fat were unaltered. Under HFHS chow, Gal-9−/− mice receiving Gal-9−/− or Gal-9wt/wt bone marrow-derived cells (BMCs) demonstrated significantly lower body weight compared with Gal-9wt/wt mice receiving Gal-9−/− BMCs. We identified the binding between Gal-9 and peroxiredoxin-2 (PRDX2) in sugar chain-independent manner by nanoLC-MS/MS, immunoprecipitation, and pull-down assay. In 3T3L1 adipocytes, Gal-9 knockdown shifts PRDX2 monomer (reduced form) dominant from PRDX2 dimer (oxidized form) under oxidative stress with H2O2. The inhibition of Gal-9 in adipocytes may be a new therapeutic approach targeting the oxidative stress and subsequent glucose intolerance in obesity. |
url |
https://doi.org/10.1038/s41598-021-85080-1 |
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